Target-dependent parameter-effect landscapes of low-intensity focused ultrasound neuromodulation in humans: a systematic review

Transcranial low-intensity focused ultrasound (LIFU) offers a rare ability to noninvasively modulate human brain activity in superficial and deep neural structures. Yet the field still cannot reliably predict how a given acoustic protocol will affect a specific brain target. We synthesize 230 LIFU experiments targeting the human cerebrum from 136 articles reporting sufficient acoustic information and neuromodulatory outcomes. We compare associations between acoustic parameters and reported outcomes across cortical and subcortical targets. This reveals divergent parameter-effect landscapes across cortical and subcortical targets. Cortical outcomes follow a nonmonotonic organization across pulse repetition frequency and duty cycle, with distinct zones associated with facilitation, suppression, and null or ambiguous effects. Subcortical outcomes instead vary predominantly along duty cycle, shifting from suppression at lower values toward facilitation at higher values. Intensity and dose factors do not provide a consistent target-independent explanation for outcome polarity, and current evidence is insufficient to identify parameters promoting lasting effects. These findings challenge the assumption that acoustic protocols have generalizable effects across the brain and identify anatomical target as a central dimension that should inform LIFU protocol design. We provide SonoMap, an open, interactive web resource that supports a more systematic, evidence-based approach to human LIFU neuromodulation.